Dissolution of solid drugs

Whether the solution process takes place in the laboratory or in vivo, there is one law which defines the rate of solution of solids when the process is diffusion-controlled and involves no chemical reaction. This is the 

Rguie 1.15 Schematic diagram of dissolution from a solid surface. 

Tabb 1.6 How the parameters of the dissolution equation can be changed to increase (+) or decrease (-) the rate of solution  

Equation parameter Comments Effect on rate of solution 

D (diffusion coefficient of drug) May be decreased in presence of substances which increase viscosity of the medium (-) 

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Type of solution (aqueous vs. lipid) Rate of dissolution of solid drugs Concentrations of a drug present Blood flow to the site of absorption Surface area of absorption... 

While surfactants in submicellar concentrations, are used to promote the dissolution of solid drug particles by wetting surfaces and thus making them accessible for the aqueous solvent phase, they act as micellar carriers in concentrations above the CMC as described. Moreover under certain conditions, in still higher concentrations they... 

Dissolution of solid drug must occur prior to the drug release process. 

P Singh, S Desai, D Flanagan, A Simonelli, W Higuchi. Mechanistic study of the influence of micelle solubilization and hydrodynamic factors on the dissolution rate of solid drugs. J Pharm Sci 57 959, 1968. 

Equations (25) and (26) show that the dissolution number will also influence the drug absorption in addition to the absorption and dose numbers. Assuming that the initial amount of drug in solution is insignificant compared to the amount of solid drug, the fraction of dose absorbed can be estimated by... 

Mooney et al. [70] investigated the effect of pH on the solubility and dissolution of ionizable drugs based on a film model with total component material balances for reactive species, proposed by Olander. McNamara and Amidon [71] developed a convective diffusion model that included the effects of ionization at the solid-liquid surface and irreversible reaction of the dissolved species in the hydrodynamic boundary layer. Jinno et al. [72], and Kasim et al. [73] investigated the combined effects of pH and surfactants on the dissolution of the ionizable, poorly water-soluble BCS Class II weak acid NSAIDs piroxicam and ketoprofen, respectively. 

In vitro dissolution testing is an important tool in the development of solid drug products, as well as in batch quality controls. The aim of the test is to see that the drug is appropriately dissolved in the gastrointestinal tract and made available for absorption. It is therefore highly desirable that the in vitro tests provide data that correlate to the in vivo situation. However, attainment of IVIVC has often failed-and the concept of IVIVC has been challenged. 

Evaluation of the dissolution rates of solid drugs is extremely important in the development, formulation, and quality control of solid pharmaceuticals. The... 

Since the rate of absorption of many drugs from the gastrointestinal tract is controlled by their dissolution rate, this becomes the rate-limiting step. Accurate and reliable measurements of dissolution rate are therefore required in the pharmaceutical sciences. The measurement and interpretation of the dissolution rates of solid drugs in the pure state or from formulations, such as tablets, capsules, and suppositories, has an extensive pharmaceutical literature [95-100]. Moreover, the design, operation, and interpretation of dissolution rate measurements on pharmaceutical solids have been the subject of considerable scientific study, technical development, and debate. 

Dissolution testing, a routine requirement for tablets and capsules, is one of the most frequently performed tests in the pharmaceutical laboratory. It measures the dissolution of active drugs from solid dosage forms under standardized conditions. It is a tedious and... 

Sjoekvist, E., C. Nystroem, and M. Alden. 1991. Physicochemical aspects of drug release. XIII. The effects of sodium dodecyl sulfate additions on the structure and dissolution of a drug in solid dispelrclailis. Pharm.69 53-62. 

The Noyes-Whitney equation forthe dissolution of solids into a solvent (Noyes and Whitney, 1897) can be used to calculate the rate of drug concentrati iin Dease with time jjt... 

For dissolution of solid particles, the Hixson-Crowell cube-root law (Eq. 5.3) assumes that the thickness of the diffusion layer h is constant during dissolution. However, this is not necessarily true. In addition, most drug particles are nonspherical and nonuniform in size. Therefore, very often the dissolution mechanism of solid drug particles is actually much more complicated. Nevertheless, the Hixson-Crowell cube-root law provides the first approximation to model powder dissolution. 

NOTE The values in this table suggest that dissolution rate (or release rate) can be modified significantly by the solubility and particle size of solid drug particles. 

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